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World Journal of Emergency Medicine ›› 2023, Vol. 14 ›› Issue (5): 367-371.doi: 10.5847/wjem.j.1920-8642.2023.078

• Original Article • Previous Articles     Next Articles

Mendelian randomization study to investigate the causal relationship between plasma homocysteine and chronic obstructive pulmonary disease

Yanlan Hu1, Ping Tan2, Juntao Wang1, Jun Zeng3, Quan Li4, Shijiao Yan1,5, Wenjie Hao1, Lanfen He1, Xingyue Song5, Caihong Zhang6(), Chuanzhu Lyu3,7,8()   

  1. 1International School of Public Health and One Health, Hainan Medical University, Haikou 571199, China
    2Department of Emergency Medicine, Hunan Provincial People’s Hospital/the First Affiliated Hospital, Hunan Normal University, Changsha 410002, China
    3Emergency Medicine Center, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu 610072, China
    4Emergency Department, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing 100730, China
    5Department of Emergency, Hainan Clinical Research Center for Acute and Critical Diseases, the Second Affiliated Hospital of Hainan Medical University, Haikou 570100, China
    6International School of Nursing, Hainan Medical University, Haikou 570100, China
    7Key Laboratory of Emergency and Trauma of Ministry of Education, Hainan Medical University, Haikou 570100, China
    8Research Unit of Island Emergency Medicine, Chinese Academy of Medical Sciences (No. 2019RU013), Hainan Medical University, Haikou 570100, China
  • Received:2023-03-20 Accepted:2023-07-16 Online:2023-10-30 Published:2023-09-01
  • Contact: Caihong Zhang, Email: 404669792@qq.com; Chuanzhu Lyu, Email: lvchuanzhu677@126.com

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Abstract:

BACKGROUND: Several observational studies have shown an association between homocysteine (Hcy) levels and chronic obstructive pulmonary disease (COPD), but causal relationships are not clear. Our study aimed to explore the causal relationship between plasma Hcy and COPD by two-sample Mendelian randomization (MR).
METHODS: A two-sample MR study was performed to infer the causal link. Genetically predicted plasma Hcy was selected as an instrumental variable (IV) from published genome-wide association study (GWAS) meta-analyses. COPD with different etiologies was extracted as outcome variables from other GWAS meta-analyses. The main MR analysis was performed using the inverse-variance weighted (IVW) method. Additional analyses were further performed using Cochran's Q-test and MR-Egger regression to evaluate the heterogeneity or horizontal pleiotropy of our findings.
RESULTS: MR analysis showed no significant association between plasma Hcy and COPD. The results of the groups were consistent with the sensitivity analysis and repeated analysis, without heterogeneity or horizontal pleiotropy. The IVW results showed COPD hospital admissions (odds ratio [OR] 1.06, 95% confidence interval [CI] 0.91-1.24, P=0.42), asthma/COPD (OR 0.97, 95% CI 0.89-1.06, P=0.55), COPD-related chronic infection (OR 1.50, 95% CI 0.57-3.99, P=0.41), COPD/asthma/interstitial lung disease (ILD)-related pneumonia or pneumonia-derived septicemia (OR 0.93, 95% CI 0.86-1.02, P=0.13), and COPD-related respiratory insufficiency (OR 1.00, 95% CI 0.7-1.44, P=0.99).
CONCLUSION: There is no direct causal relationship between plasma Hcy and COPD in our study. As Hcy is known to have deleterious effects on endothelial function and vascular homeostasis, further studies are needed to investigate whether additional factors mediate the association between Hcy and COPD.

Key words: Homocysteine, Chronic obstructive pulmonary disease, Mendelian randomization